Search

Background Aortic valve stenosis (AVS) is currently the most common heart valve disease. The results of observational studies on the incidence of AVS in the renal dysfunction population are contradictory due to the short follow-up period and different diagnostic criteria, etc. This study aimed to explore the causal relationship between kidney function and AVS using Mendelian randomization (MR) analysis.Methods We acquired summary statistics of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) from the CKDGen Consortium and a study on AVS from the FinnGen biobank. Univariate and multivariable MR analyses were conducted to evaluate the causal associations. The MR-Egger intercept and MR-PRESSO Global test were applied to assess the pleiotropic effects. The heterogeneity of MR results was tested by Cochran’s Q statistic. Moreover, the Bonferroni and FDR corrections were performed for multiple tests.Results Genetically predicted decreased eGFR may be associated with a raised risk of AVS (OR = 0.045, p = 1.317e-04 by IVW; OR = 0.002, p = 0.004 by MR-Egger, OR = 0.091, p = 0.057 by WM). The causal association still established after multiple comparisons. Quality control analyses indicated the absence of heterogeneity and pleiotropy in our MR research. In addition, the causality of eGFR and AVS remained significant in multivariable MR analysis after adjusting BMI, hypertension, T2DM, LDL-C, and smoking.Conclusion Our MR study discovered that reduced eGFR may be a causative risk factor for AVS. In addition, the evidence did not support a significant causal association of AVS on kidney function.

Abstract The joint utilization of the Fifth Generation Communications Technology (5G) and the Global Navigation Satellite System (GNSS) serves as a promising solution to address the challenges associated with insufficient visible satellites and lower observation quality in urban environments. 5G allows for the angle and distance measurements, augmenting the performance of Real-Time Kinematic (RTK) positioning. To quantify the improvement of 5G observations on RTK positioning, this paper proposes a float solution gain factor and the Ambiguity Dilution of Precision (ADOP) gain factor. Based on these gain factors, the theoretical analysis and simulation are performed. This study designs an extended Kalman filter for 5G-assisted BeiDou Navigation Satellite System (BDS) RTK positioning, employing both the Full Ambiguity Resolution (FAR) and Partial Ambiguity Resolution (PAR) modes. Our experiment verified the effectiveness of 5G-assisted BDS RTK positioning in mitigating outlier occurrences and improving the ambiguity fixing rate as well as the positioning accuracy. In the FAR and PAR modes, the Three-Dimensional (3D) spatial accuracy increased by 48% and 18.8%, respectively, and the results are consistent with theoretical analysis based on gain factors. The fixing rate of RTK increased from 11.11% to 13.93%, while it increased from 32.58% to 44.43% for the PAR mode. The assistance of 5G observations reduced the median error for the FAR mode from over 1.3m to 0.9 m, and the third quartile from 2.1m to 1.05 m. For the PAR mode, the median error decreased from 0.5m to 0.12 m, and the third and fourth quartiles decreased from 0.65m to 0.38 m.

Abstract Background Aortic valve stenosis (AVS) is the most prevalent cardiac valve lesion in developed countries, and pathogenesis is closely related to aging. DNA methylation-based epigenetic clock is now recognized as highly accurate predictor of the aging process and associated health outcomes. This study aimed to explore the causal relationship between epigenetic clock and AVS by conducting a bidirectional Mendelian randomization (MR) analysis. Methods Summary genome-wide association study statistics of epigenetic clocks (HannumAge, HorvathAge, PhenoAge, and GrimAge) and AVS were obtained and assessed for significant instrumental variables from Edinburgh DataShare (n = 34,710) and FinnGen biobank (cases = 9870 and controls = 402,311). The causal association between epigenetic clock and AVS was evaluated using inverse variance weighted (IVW), weighted median (WM), and MR-Egger methods. Multiple analyses (heterogeneity analysis, pleiotropy analysis, and sensitivity analysis) were performed for quality control assessment. Results The MR analysis showed that the epigenetic age acceleration of HorvathAge and PhenoAge was associated with an increased risk of AVS (HorvathAge: OR = 1.043, P = 0.016 by IVW, OR = 1.058, P = 0.018 by WM; PhenoAge: OR = 1.058, P = 0.005 by IVW, OR = 1.053, P = 0.039 by WM). Quality control assessment proved our findings were reliable and robust. However, there was a lack of evidence supporting a causal link from AVS to epigenetic aging. Conclusion The present MR analysis unveiled a causal association between epigenetic clocks, especially HorvathAge and PhenoAge, with AVS. Further research is required to elucidate the underlying mechanisms and develop strategies for potential interventions. Graphical abstract

BackgroundPancreatic cystic neoplasms are increasingly diagnosed with the development of medical imaging technology and people’s self-care awareness. However, two of their sub-types, serous cystic neoplasms (SCN) and mucinous cystic neoplasms (MCN), are often misclassified from each other. Because SCN is primarily benign and MCN has a high rate of malignant transformation. Distinguishing SCN and MCN is challenging and essential.PurposeMRIs have many different modalities, complete with SCN and MCN diagnosis information. With the help of an artificial intelligence-based algorithm, we aimed to propose a multi-modal hybrid deep learning network that can efficiently diagnose SCN and MCN using multi-modality MRIs.MethodsA cross-modal feature fusion structure was innovatively designed, combining features of seven modalities to realize the classification of SCN and MCN. 69 Patients with multi-modalities of MRIs were included, and experiments showed performances of every modality.ResultsThe proposed method with the optimized settings outperformed all other techniques and human radiologists with high accuracy of 75.07% and an AUC of 82.77%. Besides, the proposed disentanglement method outperformed other fusion methods, and delayed contrast-enhanced T1-weighted MRIs proved most valuable in diagnosing SCN and MCN.ConclusionsThrough the use of a contemporary artificial intelligence algorithm, physicians can attain high performance in the complex challenge of diagnosing SCN and MCN, surpassing human radiologists to a significant degree.

This paper addresses challenges in the application of existing colters in Chinese ecological tea plantations due to abundant straw roots and insufficient tillage depth. Aligned with the agronomic requirements of hilly eco-tea plantations, our study optimizes the structural advantages of the joint use of rotary tillage blades and double-disc colters to design an efficient trenching device. Our investigation explores the motion characteristics of a double-disc colter during deep trenching operations, in conjunction with rotary tillage blades. Employing discrete element method (DEM) simulations, this paper aims to minimize the working resistance and enhance the tillage depth stability. Single-factor experiments are conducted to determine the impact of key structural parameters on the tillage depth stability and working resistance. The optimal parameters are determined as a relative height of 80 mm to 120 mm, a 280 mm to 320 mm diameter for the double-disc colter, and a 10° to 14° angle between the two discs. The central composite design method is used to optimize the structural parameters of the double-disc colter. The results indicate that when the relative height is 82 mm, the diameter of the double-disc colter is 297 mm, and the angle between the two discs is 14°, the tillage depth stability performance reaches 91.64%. With a working resistance of merely 93.93 N, the trenching device achieves optimal operational performance under these conditions. Field validation testing shows a tillage depth stability coefficient of 92.37% and a working resistance of 104.2 N. These values deviate by 0.73% and 10.93%, respectively, from the simulation results, confirming the reliability of the simulation model. A field validation test further confirms that the operational performance of the colter aligns with the agronomic requirements of ecological tea plantations, offering valuable insights for research on trenching devices in such environments.

Abstract Aiming at the problems of high labor intensity and low efficiency in manual operation during the pulping process of rice seedling nursing in thin mud in hilly and mountain areas, this paper designed a new type of paddy field blade for seedling nursing, and utilized a rice nursery pulper to help manual operation complete the pulping process. It created a mathematical model of mud-throwing mass and operating power in the operation process of paddy field blade, and obtained the main structure factors that influenced the mud-throwing mass and operating power of paddy field blade, which included the area of mud splashing board, the angle between the front cutting edge and the mud splashing board, and the inclination angle between the front cutting surface and the mud splashing board. To further analyze the degree of influence of the blade’s main structure parameters on mud-throwing mass and operating power, it used EDEM discrete element simulation software to establish a discrete element simulation model of paddy field blade and mud particle system, performed simulation analysis with the method of orthogonal experimental design, and conducted a bench test for comparison. The results showed that: (1) the degree of influence of the three structure parameters on mud-throwing mass and operating power from large to small in order was the area of mud splashing board > the inclination angle between front cutting surface and mud splashing board > the angle between front cutting edge and mud splashing board; (2) the maximum relative error for mud-throwing mass between simulation analysis and bench test was 4.53%, and that for operating power was 8.67%; and (3) three reference parameters combinations were selected by P2-1/M2 graph, the mud-throwing mass of the three combinations was 40.43%, 27.52% and 0.16% higher than that of the original blade, and the power consumed was 13.99%, 21.83% and 36.65% lower than that of the original blade, indicating that the new paddy field blade had good operating performance.

The purpose of this study was to address the problem of the poor quality of rotary cutting and soil collection during the process of mechanical ridge building in paddy fields. In order to improve the soil collection rate and decrease the coefficient of variation of soil collection uniformity, the present work mainly combined the advanced rotary-cutting and tillage technology and the rotary-cutting soil collection device, at domestic and international, to study the motion characteristics and distribution situation of soil particles during rotary-cutting and soil collection operations. The test of rotary-cutting soil collection device was simulated by using the EDEM2018 Version: 4.0.0, the accuracy of numerical model was validated by the data of trial test. The results of the single-factor experiment indicated that the working speed level of the rotary blades was 450 r/min to 550 r/min, the operating speed level of the rotary blades was 0.6 km/h to 1.0 km/h, and the tilling depth level of the rotary blades was 180 mm to 200 mm. Moreover, the operating parameter of the rotary-cutting soil collection device were obtained by a multi-factor test, and it was proved that the rotary-cutting soil collection device performed better and the soil collection quality was higher, with a soil collection rate and a coefficient of variation of soil collection uniformity of 87.22% and 6.73%. This study could provide technical support for the research of rotary tillage devices and improve the level of mechanized ridge building in paddy fields.

Reperfusion is essential for ischemic myocardium but paradoxically leads to myocardial damage that worsens cardiac functions. Ferroptosis often occurs in cardiomyocytes during ischemia/reperfusion (I/R). The SGLT2 inhibitor dapagliflozin (DAPA) exerts cardioprotective effects independent of hypoglycemia. Here, we investigated the effect and potential mechanism of DAPA against myocardial ischemia/reperfusion injury (MIRI)-related ferroptosis using the MIRI rat model and hypoxia/reoxygenation (H/R)-induced H9C2 cardiomyocytes. Our results show that DAPA significantly ameliorated myocardial injury, reperfusion arrhythmia, and cardiac function, as evidenced by alleviated ST-segment elevation, ameliorated cardiac injury biomarkers including cTnT and BNP and pathological features, prevented H/R-triggered cell viability loss in vitro. In vitro and in vivo experiments showed that DAPA inhibited ferroptosis by upregulating the SLC7A11/GPX4 axis and FTH and inhibiting ACSL4. DAPA notably mitigated oxidative stress, lipid peroxidation, ferrous iron overload, and reduced ferroptosis. Subsequently, network pharmacology and bioinformatics analysis suggested that the MAPK signaling pathway was a potential target of DAPA and a common mechanism of MIRI and ferroptosis. DAPA treatment significantly reduced MAPK phosphorylation in vitro and in vivo, suggesting that DAPA might protect against MIRI by reducing ferroptosis through the MAPK signaling pathway.

Cell replacement therapy using neural progenitor cells (NPCs) has been shown to be an effective treatment for ischemic stroke. However, the therapeutic effect is unsatisfactory due to the imbalanced homeostasis of the local microenvironment after ischemia. Microenvironmental acidosis is a common imbalanced homeostasis in the penumbra and could activate acid-sensing ion channels 1a (ASIC1a), a subunit of proton-gated cation channels following ischemic stroke. However, the role of ASIC1a in NPCs post-ischemia remains elusive. Here, our results indicated that ASIC1a was expressed in NPCs with channel functionality, which could be activated by extracellular acidification. Further evidence revealed that ASIC1a activation inhibited NPC migration and neurogenesis through RhoA signaling-mediated reorganization of filopodia formation, which could be primarily reversed by pharmacological or genetic disruption of ASIC1a. In vivo data showed that the knockout of the ASIC1a gene facilitated NPC migration and neurogenesis in the penumbra to improve behavioral recovery after stroke. Subsequently, ASIC1a gain of function partially abrogated this effect. Moreover, the administration of ASIC1a antagonists (amiloride or Psalmotoxin 1) promoted functional recovery by enhancing NPC migration and neurogenesis. Together, these results demonstrate targeting ASIC1a is a novel strategy potentiating NPC migration toward penumbra to repair lesions following ischemic stroke and even for other neurological diseases with the presence of niche acidosis.

BackgroundAlthough increasing evidence has reported an increased risk of atherosclerosis (AS) in rheumatoid arthritis (RA), the communal molecular mechanism of this phenomenon is still far from being fully elucidated. Hence, this article aimed to explore the pathogenesis of RA complicated with AS.MethodsBased on the strict inclusion/exclusion criteria, four gene datasets were downloaded from the Gene Expression Omnibus (GEO) database. After identifying the communal differentially expressed genes (DEGs) and hub genes, comprehensive bioinformatics analysis, including functional annotation, co-expression analysis, expression validation, drug-gene prediction, and TF-mRNA-miRNA regulatory network construction, was conducted. Moreover, the immune infiltration of RA and AS was analyzed and compared based on the CIBERSORT algorithm, and the correlation between hub genes and infiltrating immune cells was evaluated in RA and AS respectively.ResultsA total of 54 upregulated and 12 downregulated communal DEGs were screened between GSE100927 and GSE55457, and functional analysis of these genes indicated that the potential pathogenesis lies in immune terms. After the protein-protein interaction (PPI) network construction, a total of six hub genes (CCR5, CCR7, IL7R, PTPRC, CD2, and CD3D) were determined as hub genes, and the subsequent comprehensive bioinformatics analysis of the hub genes re-emphasized the importance of the immune system in RA and AS. Additionally, three overlapping infiltrating immune cells were found between RA and AS based on the CIBERSORT algorithm, including upregulated memory B cells, follicular helper T cells and γδT cells.ConclusionsOur study uncover the communal central genes and commonness in immune infiltration between RA and AS, and the analysis of six hub genes and three immune cells profile might provide new insights into potential pathogenesis therapeutic direction of RA complicated with AS.

Changes in meteorological conditions affect crop output and planting structure. Based on county-level data of agricultural statistics and weather information in Guangdong province from 1992 to 2018, this paper uses a panel regression model to examine the effects of high impact weather on agricultural outputs and identify the responses in planting structure. The findings show that the rainstorm significantly reduces the per-unit yield (PUY) of rice, and an additional day with daily excessive precipitation (≥50 mm) in the growth period leads to an average 0.25% reduction in PUY. However, the vegetable yield is not susceptible to high-impact weather. With a two-period panel regression model and sub-regional climate response analysis, we find that the agricultural planting structure is formed by the regional farming adapting to the high-impact weather (low temperature, high temperature, rainstorms, and high wind). The original rice farmland in the more climate-sensitive areas is transformed into vegetable farming, while the scale of rice is increasing in those less sensitive areas. Finally, we argue that the agricultural sector should assess the impacts of climate change on staple crops and make national climate sensitivity zoning maps. It will provide a scientific justification for making the national agriculture structural adjustment plan.

Abstract Stereo matching, which is a key problem in computer vision, faces the challenge of radiometric distortions. Most of the existing stereo matching methods are based on simple matching cost algorithms and appear the problem of mismatch under radiometric distortions. It is necessary to improve the robustness and accuracy of matching cost algorithms. A novel encoding pattern is proposed for stereo matching. In the proposed encoding pattern, each of the matching windows in the grey image and gradient images is divided into several isoline‐like sets with different radii. Then, pixel pairs are defined in the isoline‐like sets. An encoding function is used to decide the relative order between the two pixels in each pixel pair. To apply the pattern for matching cost computation and enhance the matching accuracy, an adaptively weighted cost is designed that is related to the isoline‐like sets. Experiments are conducted on the Middlebury and KITTI data sets to show the validity of the proposed method under severe radiometric distortions. Also, the comparisons with some widely used methods are made in the experiments to illustrate the advantage of the proposed method.

Acute myocardial infraction is the most severe type of coronary artery disease and remains a substantial burden to the health care system globally. Although myocardial reperfusion is critical for ischemic cardiac tissue survival, the reperfusion itself could cause paradoxical injury. This paradoxical phenomenon is known as ischemia–reperfusion injury (IRI), and the exact molecular mechanism of IRI is still far from being elucidated and is a topic of controversy. Meanwhile, ferroptosis is a nonapoptotic form of cell death that has been reported to be associated with various cardiovascular diseases. Thus, we explored the potential ferroptosis mechanism and target in cardiac IRI via bioinformatics analysis and experiment. GSE4105 data were obtained from the GEO database and consist of a rat IRI model and control. After identifying differentially expressed ferroptosis-related genes (DEFRGs) and hub genes of cardiac IRI, we performed enrichment analysis, coexpression analysis, drug–gene interaction prediction, and mRNA–miRNA regulatory network construction. Moreover, we validated and explored the multitemporal expression of hub genes in a hypoxia/reoxygenation (H/R)-induced H9C2 cell injury model under different conditions via RT-qPCR. A total of 43 DEFRGs and 7 hub genes (tumor protein p53 [Tp53], tumor necrosis factor [Tnf], hypoxia-inducible factor 1 subunit alpha [Hif1a], interleukin 6 [Il6], heme oxygenase 1 [Hmox1], X-box binding protein 1 [Xbp1], and caspase 8 [Casp8]) were screened based on bioinformatics analysis. The functional annotation of these genes revealed apoptosis, and the related signaling pathways could have association with the pathogenesis of ferroptosis in cardiac IRI. In addition, the expression of the seven hub genes in IRI models were found higher than that of control under different H/R conditions and time points. In conclusion, the analysis of 43 DEFRGs and 7 hub genes could reveal the potential biological pathway and mechanism of ferroptosis in cardiac IRI. In addition, the multitemporal expression change of hub genes in H9C2 cells under different H/R conditions could provide clues for further ferroptosis mechanism exploring, and the seven hub genes could be potential biomarkers or therapeutic targets in cardiac IRI.

In some contexts, rapid detection of COVID-19 from CT scans can be crucial for optimal patient management. Here, the authors present a Deep Learning system for this task with multi-center data, human reader comparison and age stratified results.

BackgroundCardiomyopathies are a heterogeneous group of heart diseases that can gradually cause severe heart failure. In particular, dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are the two main types of cardiomyopathies, yet the independent and communal biological mechanisms of both remain far from elucidated. Meanwhile, ferroptosis is a non-apoptotic form of cell death that has been proven to be associated with cardiomyopathies, but the concrete nature of the interaction remains unclear. Hence, this study explored the pathogenesis and ferroptosis mechanism of HCM and DCM via a bioinformatics analysis.MethodsSix datasets were downloaded from the Gene Expression Omnibus (GEO) database based on the study inclusion/exclusion criteria. After screening the differentially expressed genes (DEGs) and hub genes of HCM and DCM, subsequent analyses, including functional annotation, co-expression, validation, and transcription factors (TF)–mRNA–microRNA (miRNA) regulatory network construction, were performed. In addition, ferroptosis-related DEGs were also identified and verified in HCM and DCM.ResultsWe found 171 independent DEGs of HCM mainly enriched in the regulation of ERK1 and ERK2 cascade, while 171 independent DEGs of DCM were significantly involved in cell adhesion. Meanwhile, 32 communal DEGs (26 upregulated genes and 6 downregulated genes) and 3 hub genes [periostin (POSTN), insulin-like growth factor-binding protein-5 (IGFBP5), and fibromodulin (FMOD)] were determined to be shared between HCM and DCM and the functional annotation of these genes highlighted the important position of growth hormone in HCM and DCM. Moreover, we identified activating transcription factor 3 (ATF3), lysophosphatidylcholine acyltransferase 3 (LPCAT3), and solute carrier family 1 member 5 (SLC1A5) as ferroptosis-related genes in HCM and STAT3 as a ferroptosis-related gene in DCM.ConclusionThe identified independent and communal DEGs contribute to uncover a potentially distinct and common mechanism of HCM and DCM and ferroptosis-related genes could provide us with a novel direction for exploration. In addition, 3 hub genes could be potential biomarkers or therapeutic targets in patients with cardiomyopathy.

The global navigation satellite system (GNSS) has played an important role in a broad range of consumer and industrial applications. In particular, cities have become GNSS major application scenarios; however, GNSS signals suffer from blocking, reflection and attenuation in harsh urban environments, resulting in diverse received signals, e.g., non-line-of-sight (NLOS) and multipath signals. NLOS signals often cause severe deterioration in positioning, navigation, and timing (PNT) solutions, which should be identified and excluded. In this paper, we propose a vision-aided NLOS identification method to augment GNSS urban positioning. A skyward omnidirectional camera is installed on a GNSS antenna to collect omnidirectional images of the sky region. After being rectified, these images are processed for sky region segmentation, which is improved by leveraging gradient information and energy function optimization. Image morphology processing is further employed to smooth slender boundaries. After sky region segmentation, the satellites are projected onto the omnidirectional image, from which NLOS satellites are identified. Finally, the identified NLOS satellites are excluded from GNSS PNT estimation, promoting accuracy and stability. Practical test results show that the proposed sky region segmentation module achieves over 96% accuracy, and that completely accurate NLOS identification is achieved for the experimental images. We validate the performance of our method on public datasets. Compared with the raw measurements without screening, the vision-aided NLOS identification method enables improvements of 60.3%, 12.4% and 63.3% in the E, N, and U directions, respectively, as well as an improvement of 58.5% in 3D accuracy.

One of the main problems in representing information in the form of nonsystematic logic is the lack of flexibility, which leads to potential overfitting. Although nonsystematic logic improves the representation of the conventional k Satisfiability, the formulations of the first, second, and third-order logical structures are very predictable. This paper proposed a novel higher-order logical structure, named G-Type Random k Satisfiability, by capitalizing the new random feature of the first, second, and third-order clauses. The proposed logic was implemented into the Discrete Hopfield Neural Network as a symbolic logical rule. The proposed logic in Discrete Hopfield Neural Networks was evaluated using different parameter settings, such as different orders of clauses, different proportions between positive and negative literals, relaxation, and differing numbers of learning trials. Each evaluation utilized various performance metrics, such as learning error, testing error, weight error, energy analysis, and similarity analysis. In addition, the flexibility of the proposed logic was compared with current state-of-the-art logic rules. Based on the simulation, the proposed logic was reported to be more flexible, and produced higher solution diversity.

Intracerebral hemorrhage (ICH) is a destructive form of stroke that often results in death or disability. However, the survivors usually experience sequelae of neurological impairments and psychiatric disorders, which affect their daily functionality and working capacity. The recent MISTIE III and STICH II trials have confirmed that early surgical clearance of hematomas does not improve the prognosis of survivors of ICH, so it is vital to find the intervention target of secondary brain injury (SBI) after ICH. Mitochondrial dysfunction, which may be induced by oxidative stress, neuroinflammation, and autophagy, among others, is considered to be a novel pathological mechanism of ICH. Moreover, mitochondria play an important role in promoting neuronal survival and improving neurological function after a hemorrhagic stroke. This review summarizes the mitochondrial mechanism involved in cell death, reactive oxygen species (ROS) production, inflammatory activation, blood–brain barrier (BBB) disruption, and brain edema underlying ICH. We emphasize the potential of mitochondrial protection as a potential therapeutic target for SBI after stroke and provide valuable insight into clinical strategies.

Ischemic stroke has been becoming one of the leading causes resulting in mortality and adult long-term disability worldwide. Post-stroke pneumonia is a common complication in patients with ischemic stroke and always associated with 1-year mortality. Though ambroxol therapy often serves as a supplementary treatment for post-stroke pneumonia in ischemic stroke patients, its effect on functional recovery and potential mechanism after ischemic stroke remain elusive. In the present study, the results indicated that administration of 70 mg/kg and 100 mg/kg enhanced functional recovery by virtue of decreasing infarct volume. The potential mechanism, to some extent, was due to promoting NSCs differentiation into neurons and interfering NSCs differentiation into astrocytes through increasing GCase expression to activate Wnt/β-catenin signaling pathway in penumbra after ischemic stroke, which advanced basic knowledge of ambroxol in regulating NSCs differentiation and provided a feasible therapy for ischemic stroke treatment, even in other brain disorders in clinic.

Abstract Background Emerging studies have demonstrated the important physiological and pathophysiological roles of hydrogen sulphide (H2S) as a gasotransmitter for NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-associated neuroinflammation in the central nervous system. However, the effects of H2S on neuroinflammation after intracerebral haemorrhage (ICH), especially on the NLRP3 inflammasome, remain unknown. Methods We employed a Sprague–Dawley rat of collagenase-induced ICH in the present study. The time course of H2S content and the spatial expression of cystathionine-β-synthase (CBS) after ICH, the effects of endogenous and exogenous H2S after ICH, the effects of endogenous and exogenous H2S on NLRP3 inflammasome activation under P2X7 receptor (P2X7R) overexpression after ICH, and the involvement of the P2X7R in the mechanism by which microglia-derived H2S prevented NLRP3 inflammasome activation were investigated. Results We found ICH induced significant downregulation of endogenous H2S production in the brain, which may be the result of decreasing in CBS, the predominant cerebral H2S-generating enzyme. Administration of S-adenosyl-l-methionine (SAM), a CBS-specific agonist, or sodium hydrosulfide (NaHS), a classical exogenous H2S donor, not only restored brain and plasma H2S content but also attenuated brain oedema, microglial accumulation and neurological deficits at 1 day post-ICH by inhibiting the P2X7R/NLRP3 inflammasome cascade. Endogenous H2S production, which was derived mainly by microglia and above treatments, was verified by adenovirus-overexpressed P2X7R and in vitro primary microglia studies. Conclusions These results indicated endogenous H2S synthesis was impaired after ICH, which plays a pivotal role in the P2X7R/NLRP3 inflammasome-associated neuroinflammatory response in the pathogenesis of secondary brain injury. Maintaining appropriate H2S concentrations in the central nervous system may represent a potential therapeutic strategy for managing post-ICH secondary brain injury and associated neurological deficits.

In order to study the propagation laws of blasting vibration waves in weak rock tunnels, the longitudinal and circumferential blasting vibration tests in Muzhailing Tunnel were carried out, and the measured data were analyzed and studied using the methods of Sadov’s nonlinear regression, Fourier transform, and Hilbert–Huang transform (HHT) to provide a reference for the optimization of blasting design of Muzhailing Tunnel or similar weak rock tunnels. The results showed that the tangential main frequency decreases rapidly and the radial main frequency decreases slowly with the increase of proportionate charge quantity. Under a certain charge quantity, as the distance from the explosion source increases, the spectrum width of the blasting vibration frequency becomes narrower, the overall energy is more concentrated, and the vibration frequency tends to be closer to the low frequency. At a certain distance from the explosive source, the frequency of blasting vibration decreases gradually, and the amplitude of low-frequency region increases with the increase of charge quantity. The vibration velocity on the left side of the tunnel is larger than that on the right side, and the vibration velocity at the vault and the arch foot of lower bench decreases rapidly, while the vibration velocity at the arch feet of upper bench and middle bench decreases slowly. The vibration frequencies of the left arch foot of the middle bench and the right arch foot of the upper bench are higher than those of other positions, while the frequencies of the left arch foot of the upper bench are the lowest. During tunnel blasting, the energy input to the strata media is mainly concentrated in the stage of the blasting of the cut hole. The blasting has more energy input to the left arch foot of the upper bench and the tunnel vault, which is consistent with the conclusion of frequency analysis.

Intracerebral hemorrhage (ICH) is a devastating disease that is characterized by high morbidity and high mortality. ICH has an annual incidence of 10–30/100,000 people and accounts for approximately 10%–30% of all types of stroke. ICH mostly occurs at the basal ganglia, which is rich in nerve fibers; thus, hemiplegia is quite common in ICH patients with partial sensory disturbance and ectopic blindness. In the clinic, those symptoms are considered to originate from the white matter injury in the area, but the exact mechanisms are unknown, and currently, no effective drug treatments are available to improve the prognosis. Clarifying the mechanisms will contribute to the development of new treatment methods for patients. The transient receptor potential ankyrin 1 (TRPA1) channel is a non-selective cation channel that plays a role in inflammatory pain sensation and nociception and may be a potential regulator in emotion, cognition and social behavior. Here, we report that TRPA1 is involved in myelin damage and oxidative stress injury in a mouse ICH model. Intervention with the TRPA1 channel may be a new method to improve the motor function of patients in the early stage of ICH.

BackgroundMany previous clinical studies have demonstrated that the nigrostriatal pathway, which plays a vital role in movement adjustment, is significantly impaired after stroke, according to medical imaging and autopsies. However, the basic pathomorphological changes have been poorly investigated to date. This study was designed to explore the pathomorphological changes, mechanism, and therapeutic method of nigrostriatal impairment after intracerebral hemorrhage (ICH). Methods and ResultsIntrastriatal injection of autologous blood or microtubule depolymerization reagent nocodazole was performed to mimic the pathology of ICH in C57/BL6 mice. Immunofluorescence, Western blotting, electron microscopy, functional behavioral tests, and anterograde and retrograde neural circuit tracking techniques were used in these mice. The data showed that the number of dopamine neurons and the dopamine concentration were severely decreased and that fine motor function was impaired after ICH. Microtubule depolymerization was the main contributor to the loss of dopamine neurons and to motor function deficits after ICH, as was also proven by intrastriatal injection of nocodazole. Moreover, administration of the microtubule stabilizer epothilone B (1.5 mg/kg) improved the integrity of the nigrostriatal pathway neural circuit, increased the number of dopamine neurons (4598±896 versus 3125±355; P=0.034) and the dopamine concentration (4.28±0.99 versus 3.08±0.75 ng/mg; P=0.041), and enhanced fine motor functional recovery associated with increased acetylated α‐tubulin expression to maintain microtubule stabilization after ICH. ConclusionsOur results clarified the pathomorphological changes of the nigrostriatal pathway after ICH and found that epothilone B helped alleviate nigrostriatal pathway injury after ICH, associated with promoting α‐tubulin acetylation to maintain microtubule stabilization, thus facilitating motor recovery.

The limited-angle torque motor (LATM) is an electric actuator capable of rotating within a limited angular range and outputting a stable torque. It features a simple structure and high reliability and can be used in precise position or torque control scenarios. To reduce the torque fluctuation within the constant torque range (CTR), the effects of the stator tooth topology and size, PM magnetization direction and size, and sleeve permeability on the torque-angle characteristic of the LATM within the CTR were analyzed through FEM simulation, and the characteristics of the LATM before and after optimization were compared. Furthermore, a magneto-thermal coupling simulation of the steady-state temperature increase and thermal deformation generated by the LATM was conducted to study the effect of temperature on the LATM. The results show that the optimized LATM can output a more stable torque within the CTR and that the rated torque fluctuation rate relative to the torque at the zero position decreases by 3.2%. In addition, the temperature increase and corresponding thermal deformation of the optimized motor at 20 °C decreased by 0.22% and 0.29%, respectively.